Study of DNA-binding Proteins Using a Mechanical Nanodevice

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This project will develop a nano-device based method to study protein-DNA interactions on a single molecule basis. Specifically, the nano-device will monitor single protein binding events by detecting the conformational change induced in the probe DNA. This represents a new paradigm of molecular detection, whereby the target molecule is detected through the conformational change induced in a single-molecule probe. Molecular scale devices hold the promise to revolutionize science and technology, and demonstrating a practical single molecule device for protein detection will be a significant step in the development of the field. Scientifically, gaining insight into the interplay between molecular recognition and mechanical deformation will impact our understanding of allosteric control mechanisms in bio-polymers. Graduate students and postdoctoral fellows will be trained in state-of-the-art optical and micro-mechanical techniques to manipulate single molecules. This research cuts across disciplines and thus offers an excellent opportunity to broaden the scientific outlook of graduate students and postdoctoral researchers on current advances in molecular biophysics and nano-technology. The molecules of life - proteins, DNA - interact within the living cell in a spectacular molecular dance, where partners must find each other and direct each other's steps. Traditional methods of analysis such as X-ray crystallography examine these processes through snapshots frozen in time. The research proposed here will develop a new method to directly observe certain steps of the molecular dance as they happen in real time. Specifically, the project will employ a nano-device to observe the process of a single protein molecule interacting with a short stretch of DNA. The successful outcome of the project will, scientifically, build up our knowledge of how molecular recognition is coupled to molecular deformation in biological systems; technologically, it will demonstrate a nano-technology based platform for high-sensitivity protein detection. Graduate students and postdoctoral fellows will be trained in state-of-the-art optical and micro-mechanical techniques to manipulate single molecules. This research cuts across disciplines and thus offers an optimal opportunity to broaden the scientific outlook of graduate students and postdoctoral researchers on current advances in molecular biophysics and nano-technology.